Disposable, pre-calibrated, pre-validated sensors for use in bio-processing applications

ABSTRACT

Disposable, pre-sterilized, and pre-calibrated, pre-validated conductivity sensors are provided. These sensors are designed to store sensor-specific information, such as calibration and production information, in a non-volatile memory chip on the sensor on in a barcode printed on the sensor. The sensors are calibrated using 0.100 molar potassium chloride (KCl) solutions at 25 degrees Celsius. These sensors may be utilize with in-line systems, closed fluid circuits, bioprocessing systems, or systems which require an aseptic environment while avoiding or reducing cleaning procedures and quality assurance variances.

CROSS REFERENCE TO RELATED APPLICATION

This is a continuation-in-part of U.S. application Ser. No. 11/294,296,filed Dec. 5, 2005, incorporated by reference hereinto.

FIELD OF THE INVENTION

The invention generally relates to disposable, pre-sterilized,pre-calibrated, in-line sensors. More specifically, the inventionrelates to disposable, pre-calibrated, pre-validated probes or sensorsthat contain non-volatile memory capable of storing specificconductivity and preferably also information concerning the “out-of-box”performance of the probe or sensor.

BACKGROUND OF THE INVENTION

Pre-sterilized, single-use bag manifolds such as those used inbio-pharmaceutical production (see U.S. Pat. No. 6,712,963, incorporatedhere by reference) lack the ability to monitor and validate important,analytical solution parameters during the processing ofbiopharmaceutical solutions. The use of such bag manifolds, for example,in preparative chromatography or tangential flow filtration (TFF) orfluid transfer generally, is severely limited by the general lack ofpre-sterilized, pre-calibrated, pre-validated in-line sensors anddetectors

In-line, flow through-type sensors and detectors are well known inindustry and are extensively used in analytical laboratories, pilotplants and production facilities. In-line conductivity detectors, inparticular, are used in ion chromatography, preparative chromatography,flow injection analysis (FIA), tangential flow filtration (TFF), as wellas water purity analysis. However, prior-art in-line flow throughconductivity sensors and detectors are typically made out of machined,stainless steel or plastic materials. These sensors and detectors areintended for permanent installations and long-term use. Prior-artin-line sensors and detectors are difficult to sterilize, requirein-field calibration and validation by an experienced operator beforeuse, and are very expensive, often costing thousands of dollars.Consequently, prior art sensors and detectors are not suited for asingle-use sensor application.

The use of a memory device imbedded in disposable clinical sensors hasbeen reported. For example, U.S. Pat. No. 5,384,028 deals with thefabrication of an enzyme-based glucose biosensor that utilizes asensor-imbedded data memory device. However, this patent utilizesbarcodes and memory devices for purposes of sensor traceability andinventory control. Furthermore, this patent requires sensor calibrationand/or validation by the clinician immediately prior to each use.

In line sensors for use in bioprocessing applications must be designedto meet government regulations regarding device traceability andvalidation. In addition, in-line sensors must meet the applicationrequirements for accuracy and precision. These requirements presentextra challenges and pose unique problems when the in-line sensor is tobe disposable and suitable for single use as desired. Another problem ishow to provide disposable in-line sensors that are pre-calibrated. Alsofor aseptic sensor applications, each single-use sensor, must meetsterilization requirements. Furthermore, single-use sensors must meeteconomic requirements, i.e. sensors must be low cost, easy to replacewith negligible disposal expense.

Meeting sensor sterilization requirements represents another verysignificant sensor design challenge. This is especially the case, whenthe sensor is intended for single-use bag manifold applications such asthose described in the U.S. Pat. No. 6,712,963 (which is incorporatedherein by reference). The biotechnology and bio-pharmaceuticalindustries utilizes four different sterilization methods: (1)autoclaving (i.e. timed exposure to pressurized steam at approximately125° Celsius); (2) time-limited exposure to an ethylene oxide gas; (3)gamma ray irradiation up to 50 kGy; and (4) electron-beam irradiation.

For many single-use sensor application, e.g. for bag manifolds, thepreferred sterilization method by the industry is by gamma orelectron-beam irradiation. The main advantage of gamma and electron-beamirradiation lies is that the entire, pre-assembled manifold, includingbags, tubing, connectors and sensors, can be first sealed in a shippingbag and then exposed to sterilizing radiation or electron-beambombardment. The entire manifold assembly within the shipping bagremains sterile for a rated period, unless the shipping bag is comprisedduring shipment or storage.

SUMMARY OF THE INVENTION

The present invention overcomes the aforementioned shortcomings andproblems faced by the industry by providing a low-cost, pre-sterilized,pre-calibrated, in-line sensor capable of being traced and validated.The invention further provides a barcode or other printed means, and/ora sensor-embedded, non-volatile memory chip for storing device-specificinformation for instant recall by the user.

The preferred embodiment is an in-line conductivity sensor system usedto measure the conductivity of the process flow solution. The presentembodiment has two main components: the user interface and the sensorassembly module.

The sensor assembly module contains a short tubular fluid conduit, oneor more sensor or probe components, referred to herein at times as asensor or a sensor component. The sensor assembly module furtherincludes a printed circuit board (PCB) with a sensor-embeddednon-volatile memory chip. Sensor components can include electrodes,toroidal sensors or other arrangements. All components are designed orselected for highly automated production methods such as those used insurface mounted electronic assemblies. The present disclosure focuses onmultiple electrode arrangements as the preferred embodiment for carryingout the sensing function.

In the illustrated preferred embodiment, four electrodes arepress-fitted into and through four, linearly arranged holes in the fluidconduit wall. The electrodes are epoxied, cemented or sealed into placeto prevent leaks or contamination. The electrodes are connected to aPCB. The PCB contains a thermistor, in thermal contact with two of theconductivity electrode pins. The PCB also contains a non-volatile memorychip or EEPROM, which is used to store sensor-specific information,which typically includes the sensor's ID number, a Cell Constant, aTemperature Offset Value, and the calibration date.

Furthermore, each sensor has an “out-of-box” performance variance valuewhich is also stored in the non-volatile memory chip. This “out-of-box”value is a statistically derived performance variance (measured forexample in 0.100 molar KCl at 25.0° C.) that represents the maximummeasurement error for that specific sensor within a 98% confidencelimit. The statistically derived variance value is based on theperformance analysis of all calibrated sensors within a production run,typically of between about 100 and about 500 sensors. The factorydetermined performance variance represents a predictive, “out-of-box”sensor performance level.

The user interface performs the conductivity measurement by monitoringthe current across the two inner working electrodes. Prior to theconductivity measurement, the user interface retrieves the Cell Constantfrom its own memory (after it has decoded the barcode and retrieved thatinformation) or from the sensor memory. The measured solutionconductance is multiplied by the Cell Constant to arrive at the actualconductivity of the tested process solution. The sensor-specific CellConstant is determined during factory calibration using a solution (forexample 0.100 molar KCl at 25.0° C.) with a known conductivity. The CellConstant is subsequently stored in the non-volatile memory of the sensorassembly module.

Typically, after the sensor module is prepared, it is placed in ashipping bag and then sterilized. The sensor may be sterilized by any ofthe different sterilization methods utilized in the biotechnology,bio-pharmaceutical or medical industries. However, it has been foundthat when the sensor assembly modules are exposed to gamma ray andelectron-beam irradiation, the irradiation erases or destroys thenon-volatile memory chip or EEPROM. Thus, the sensor assembly module ofthe present invention is equipped with means for storing sensor specificinformation that is unaffected by gamma ray and electron-beamirradiation.

It is a general aspect or object of the present invention to provide adisposable conductivity sensor.

Another aspect or object of the present invention is to provide adisposable sensor suitable for one-time use, which may be integratedwith other disposable equipment, including bag manifolds, employed inthe separation and purification of fluids that are suitable forsingle-use applications.

An aspect or object of the present invention is to reduce the costassociated with the construction of conductivity sensors.

Another aspect or object of the present invention is to provide a sensorhaving a stored “out-of-box” performance variance value.

Another aspect or object of the present invention is to provide a Sensorhaving a means to store sensor specific information, which is notaffected by gamma ray or electron-beam irradiation techniques.

These and other objects, aspects, features, improvements and advantagesof the present invention will be clearly understood through aconsideration of the following detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an illustration of a preferred embodiment of the userinterface and of the conductivity sensor assembly that is attached atboth ends of a fluid conduit of a fluid transfer system;

FIG. 2 is a cut-away perspective view of the illustrated conductivitysensor assembly;

FIG. 3 is an exploded perspective view illustration of the illustratedconductivity sensor and the fluid conduit;

FIG. 4 a is a perspective view of the component side of the illustratedconductivity sensor;

FIG. 4 b is a perspective view of the underside of the illustratedconductivity sensor;

FIG. 5 a is a plan view of the underside of another embodiment of aconductivity sensor;

FIG. 5 b is an elevation view of the conductivity sensor of FIG. 5 a;FIG. 5 c is a plan view of the component side of the conductivity sensorof FIG. 5 a;

FIG. 6 is a schematic circuit diagram of the illustrated conductivitysensor;

FIG. 7 is an illustration of a sensor with barcodes for storing sensorspecific information;

FIG. 8 is an illustration of a user interface connected to a barcodereader for reading the sensor specific information from the barcodeslocated on the sensor assembly; and

FIG. 9 is a flowchart illustrating the lifecycle of a sensor.

DETAILED DESCRIPTION OF THE EMBODIMENTS

As required, detailed embodiments of the present invention are disclosedherein; however, it is to be understood that the disclosed embodimentsare merely exemplary of the invention, which may be embodied in variousforms. Therefore, specific details disclosed herein are not to beinterpreted as limiting, but merely as a basis for the claims and as arepresentative basis for teaching one skilled in the art to variouslyemploy the present invention in virtually any appropriate manner.

A system designed to measure the conductivity of fluids in a closedfluid system by using a pre-calibrated disposable in-line conductivitysensor is shown in FIG. 1. The conductivity sensor assembly is generallydesignated as 100. The assembly 100 is designed to be integrable with afluid circuit and to be disposable. Contained with the conductive sensorassembly 100 is a short tubular fluid conduit 102, designed for aparticular manifold flow rate range of the fluid circuit. Typically, thefluid conduit 102 is tubular and has a diameter between about 3 mm andabout 25 mm (about ⅛ inch and about 1 inch). The flow conduit 102 ismade of a polymer such as a polyolefin, for example polypropylene, butany other appropriate plastic tubing or material may be substituted. Thetubing material should be suitable for engaging and containing the fluidbeing handled, such as valuable proteins, biotechnical compositions orpharmaceutical solutions. The flow conduit 102 has molded-in fluid-tightconnections 103 and 104, which may consist of Luer, Barb, Triclover, orany connection method suitable to connect the flow conduit 102 in aprocessing system or fluid circuit, such as the illustrated polymerictubing 106. A sensing portion or conductivity sensor 108 protrudesthrough the wall of the conduit in a manner that will be more evident inthe subsequent discussion and from the drawings.

Leads such as the illustrated electrical connecting wires 110 connectthe conductivity sensor 108 to a conductivity readout device or userinterface 112. The user interface, generally designated as 112, is anycomputer like device that communicates with the sensor 108 and measuresconductivity by sending and receiving both digital and analog electricalsignals along the leads 110. The user interface 112 has a display 114 todisplay information, for example, the conductivity reading, thetemperature reading, and information stored on the conductivity sensor108 relating to the calibration, validation and tracking of the sensor.

FIG. 2 is a more detailed view of the conductivity sensor assembly 100.The housing 200 of the assembly 100 preferably is over-molded with adurable material such as a hard polyurethane polymer such as TPE. Thedurable housing material seals and protects the interior components frommoisture and outside contaminants. The sensor 108 can be furtherprotected by a sheath 202 as illustrated.

The fluid conduit 102 traverses the assembly 100 such as along its widthas illustrated. Electrodes 204 are in electrical communication with theinterior of the fluid conduit 102. In the illustrated embodiment, thefluid conduit is intersected by four electrodes of the conductivitysensor 108. These electrodes 204 can be positioned along the interior ofthe conduit 102, such as at the middle portion of the conduit.Gold-plated electrodes can be used such as ones that are about 1 mm toabout 2 mm in diameter or between about 0.025 inches to 0.05 inches indiameter. Such electrodes preferably are arranged in-line approximately2 to 2.5 mm (about 0.08 inch to 0.10 inch) apart.

In the illustrated embodiment, the electrode pins 204 are press-fittedinto and through four linearly arranged holes in the wall of the fluidconduit 102 and extend into the hollow interior of the fluid conduit102. Typical protrusion into the conduit is on the order of about 3 mmto about 13 mm (about ⅛ inch to about 0.5 inch). The electrodes 204 areepoxied, cemented or otherwise sealed to the wall of the fluid conduit102 to prevent leaks or contamination. Additionally, the electrodes 204are in electrical communication with their respective traces on thesensor 108.

In other embodiments, the electrodes 204 may only have two electrodes orpins rather than four of the preferred embodiment. In addition, theelectrodes may be constructed from other materials, such as stainlesssteel wire, titanium wire, or any other non-corrosive material.Disposability is a criteria to be considered in selecting these or anyother materials of the device.

FIG. 3 shows a component view of the fluid conduit 102, sensor 108, andsheath 202. The illustrated sheath 202 has a top portion 302 and abottom portion 304. The illustrated electrodes 204 are press-fitted intoand through the wall of the fluid conduit 102 and are connected to theprinted circuit board (PCB) 306 of the conductivity sensor 108. Thepreferred PCB 306 is a double sided PCB with conductive solder traces.Each pin of the electrodes 204 is in direct contact with its respectivetrace, and each is shown soldered onto the printed circuit board (PCB)306.

Opposite the electrodes 204, the PCB 306 is wedged between two rows offive pins of a miniature, 8-pin DIN connector 308. These five pins ofthe DIN connector 308 are in direct contact with the PCB 306 and aresoldered to the PCB 306. The three remaining pins of the DIN connector308 are wired and soldered to the PCB 306. The end of the sensor 1081 scapped and sealed by the cap-ring 310. The DIN connector 308 isdetachably connected to the user interface 112 by the connecting wires110. Each pin of the DIN connector 308 is associated with an individualwire of the connecting wires 110.

FIG. 4 a shows the top view or the component view of the sensor 108. Theelectrodes 204 are connected to the underside of the PCB 306. Asurface-mounted thermistor 402 is in thermal contact with two of theconductivity electrode pins when four are provided. A second, importantfunction of the thermistor is to act as a pull-up resistor for thenon-volatile memory chip, thereby assuring proper functioning of thememory device. The thermistor 402 is used to monitor the temperature ofthe solution in the fluid conduit 102, via thermal conductance, suchbeing transmitted to the user interface 112. The user interface 112reports the solution temperature data and utilizes the temperature datato correct or normalize the solution conductivity reading.

A sensor-embedded non-volatile memory chip or an EEPROM 404 is mountedon the surface of the PCB 304. The non-volatile memory chip or EEPROM404 is used to store sensor-specific information. This information canbe called up, displayed and printed out, on demand, by the userinterface 112.

The PCB 306 also contains a surface-mounted capacitor 406 that isvisible in FIG. 4 a. FIG. 4 b is an illustration of the underside of thePCB 306 in the four electrode embodiment. The electrodes 204 aresoldered to their respective traces 410, 411, 412, and 413. FIG. 4 balso further demonstrates the wedging of the PCB 306 between the pins ofthe DIN connector 308.

FIG. 5 a is a plan view of the underside of a PCB 306 a of theconductivity sensor 108 a. Hand soldered connections 501 and 502 to thePCB connect two pins 503, 504 of the 8-pin DIN connector 308 a that arenot in direct contact.

FIG. 5 b is an elevation view of the conductivity sensor 108 a. FIG. 5 balso shows how the PCB is sandwiched between the pins of the DINconnector. The low profiles of the capacitor 406 a, non-volatile memorychip 404 a and the thermistor 402 a are also evident in FIG. 5 b.

FIG. 5 c is a plan view of the conductivity sensor 108 a that is shownin FIG. 5 a and FIG. 5 b.

FIG. 6 is an electric circuit diagram illustrating the variousconnections of the sensor 108 in the preferred embodiment that isillustrated. Four connections from the 8-Pin DIN connector 308 areconnected to the four pins of the electrode 204. One pin of the DINconnector 308 provides a 5.0 Volt power supply to the capacitor 406, thenon-volatile memory chip (or EEPROM) 404, and a bi-directional serialdata line 602. One pin of the DIN connector 308 provides the ground forthe capacitor 406 and the non-volatile memory chip (or EEPROM) 404.

The non-volatile memory chip (or EEPROM) 404 uses the bi-directionserial data line 602 and a serial clock line 604 to communicate with theuser interface. Different non-volatile memory chips or EEPROMS havedifferent protocols, which are known in the art. In this embodiment, theserial data and serial clock lines allow a user interface 112 or acalibration device to read, erase, and write data to the non-volatilememory chip 404. The serial data line 602 is an open drain terminal.Therefore, the serial data line requires a pull-up resistor 606connected to the voltage source coming from the DIN connector 308. Inthis embodiment, the thermistor 402 also serves as the pull-up resistor606.

The sensor-specific information is electronically entered into thenon-volatile memory chip 404 during factory calibration of theconductivity sensor 108. The sensor-specific information may include thefollowing: Cell Constant (K), Temperature Offset, the unique Device ID,and the Calibration Date, the production lot number of the sensor, theproduction date of the sensor, the type of fluid used for calibration,the actual temperature of the fluid used, and “out-of-box” sensorperformance value.

During production, small differentiations in the electrodes 104, therespective angles of the electrodes, and the gaps between the individualelectrodes will result in different conductivity readings for eachsensor produced. These differences can significantly affect accuracy. Inkeeping with the invention, these differences are successfully addressedby having each sensor normalized or calibrated as a part of itsmanufacturing procedure.

In the illustrated example, each conductivity sensor 108 is calibratedusing certified 0.100 molar KCl (potassium chloride) solution maintainedat 25.0° C. The conductance, which is dependent on the cell geometry andthe solution resistivity, is determined by measuring the voltage dropacross the electrodes. The measured conductance together with knownsolution conductivity allows the calculation of the sensor-specific CellConstant (K). The Cell Constant (K) is determined by the followingequation:

[Solution Conductivity, (S/cm)]/[Conductance (S)]=[Cell Constant, K,(cm⁻¹)]

The sensor-specific Cell Constant (K) is then stored in the non-volatilememory 404 of the conductivity sensor 108.

For example, the solution conductivity for a 0.100 molar KCl solution isknown to be 12,850 μS (or 0.01285 S) at 25.0° C. The typical measuredconductance for a 0.100 molar KCl solution using a sensor with a ⅛ inchLuer conductivity cell with a 0.10 inch electrode separation is 0.0379Siemens. Using the equation above, the corresponding Cell Constant (K)for the particular disposable sensor of this illustration is calculatedto be 0.339 cm⁻¹.

Once the Cell Constant (K) is calculated it is stored on the sensor. Theuser interface will recall the Cell Constant (K) from the sensor. Whenundergoing normal operations, the user interface 112 measures theconductance in Siemens of the solution flowing through the fluid conduit102 by passing a current through the electrodes 204 and measuring thecurrent across the two inner electrodes 204. The user interface 112 willthen use the Cell Constant (K) for this particular disposable sensor todetermine the conductivity of the solution flowing through the fluidconduit. The user interface calculates the solution's conductivity bymultiplying the measured conductance by the Cell Constant (K), asdemonstrated in the following equation:

[Cell Constant, K, (cm⁻¹)]×[Conductance (S)][Solution Conductivity,(S/cm)]

The sensor, once calibrated, provides a linear response for NISTtraceable standard solutions ranging from 1 to 200,000 μS.

The temperature of a solution will also affect its conductivity. As aresult, the sensor must also measure and account for the temperature ofthe solution to achieve an accurate conductivity measurement.Ordinarily, un-calibrated thermistors will have a variance of ±5%between their measured reading and the actual temperature. A calibratedthermistor may achieve a variance of ±1% or less.

In this regard, a sensor-specific Temperature Offset is calibrated atthe factory. To determine the Temperature Offset, temperature readingsare made while a 25.0° C. KCl solution is pumped through the fluidconduit and over the electrodes. A comparison is then made between thetemperature reading of the un-calibrated thermistor on the sensor (Tref)with that of a NIST-traceable thermometer or thermistor (Tsen). Thedifference between the two readings is the Temperature Offset(Tref-Tsen=TempOffset). The Temperature Offset may have either apositive or a negative value. The sensor-specific Temperature Offset isthen stored in the non-volatile memory on the sensor.

Each sensor has an “out-of-box” performance variance value which is alsostored on the sensor, typically in the non-volatile memory chip. This“out-of-box” value is a statistically derived performance variance(measured in 0.100 molar KCl at 25.0° C.) that represents the maximummeasurement error for that specific sensor within a 98% confidencelimit. The statistically derived variance value is based on theperformance analysis of all calibrated sensors within a production run,typically of between about 100 and about 500 sensor assemblies. Thefactory determined performance variance represents a predictive,“out-of-box” sensor performance level. This statistical treatment isanalogous to and representative of a sensor validation procedure.Factory pre-validated conductivity sensors are thereby provided. Themeaning of “pre-validated” is further illustrated herein, including asfollows.

In the illustrated embodiment, each conductivity sensor undergoes twofactory measurements. The first measurement involves sensor calibrationand determination of the specific Cell Constant (i.e. response factor)using a 0.100 molar KCl solution at 25.0° C. as described herein. Inanother separate and distinct measurement with 0.100 molar KCl solutionat 25.0° C., the solution conductivity is experimentally determinedusing the pre-calibrated sensor. When taking into account theexperimentally derived solution conductivities for all pre-calibratedsensors, the mean conductivity value closely centers around thetheoretical value of 12,850 μS with a 3-sigma standard deviation of+/−190 μS or +/−1.5% An operator may access this information via theuser interface 112 or Conductivity Monitor.

In addition to the calibration information, such as the Cell Constant(K) and the Temperature Offset, the sensor-specific Device ID,Calibration Date, and statistical information are store in thenon-volatile memory. The Device ID is stored as a string of numbers, forexample: nn-ss-xxxx-mmyy. In this example, the variables represent thesensor lot number (nn), fluid conduit size (ss), the device serialnumber (xxxx) and the manufacturing date by month and year (mmyy). Forexample, sensor containing the Device ID of 02-02-0122-1105 means thatthis sensor was the 122^(nd) sensor made in lot 02 of conduit size 02 (afluid conduit with a diameter of ⅜″ or 9.5 mm having a barb connector),manufactured in November of 2005. In this illustration, thesensor-specific Calibration Date or the date on which the sensor wascalibrated using 0.100 molar KCl solution at 25.0° C. is also stored inthe sensor's non-volatile memory as a separate data entry.

Additionally, statistical information or statistical data about theentire lot may also be stored in the non-volatile memory. For example,the average cell constant for lot 122 may be stored in the non-volatilememory of each sensor in lot 122. The standard deviation for cellconstants for each lot may also be stored (i.e. “out-of-box” variancevalue) in the non-volatile memory of each sensor produced in that lot.This allows the user to determine whether a particular sensor is withinthe statistical range to achieve the proper margin of error for aspecific experiment or bio-processing operation. As those skilled in theart will appreciate, other known statistical methods may be utilized,the results of which may be stored in the non-volatile memory on thesensing device.

In addition to storing the Cell Constant (K), Temperature Offset, DeviceID, the Calibration Date, and other information in the non-volatilememory on the sensor, a summary of this information may be printed onthe outside of the sensor. This information may be consulted by theuser, used to later re-calibrate the sensor, and allows the user toinput the printed information directly into the user interface. Some orall the information which is stored in non-volatile memory may also beprinted or etched on to the sensor in the form of a barcode or labelcontaining a barcode.

As shown in FIG. 7, an etched or printed label 702 containing one ormore barcodes 702 a and 702 b is affixed to the exterior housing 701 ofthe sensor assembly 700. The sensor assembly has an 8-Pin DIN connector704 which operates as described above. The sensor assembly also has afluid conduit 706, designed for receiving fluids at particular manifoldflow rate range of the fluid circuit. The barcodes encode some or all ofthe sensor-specific information contained in the sensor memory device,EEPROM or memory chip. The barcodes are not affected by gamma orelectron-beam irradiation. Thus, if the sensor memory is erased, becomesnon-function, or is destroyed, the sensor-specific information isrecoverable from the barcodes affixed to the sensor housing 701 by usinga barcode reader or scanner.

As shown in FIG. 8, a handheld optical barcode scanner 300 is hooked upto a digital I/O port of the user interface device or monitor 112.Additionally, the sensor 700 is also connected to the user interface 112via the 8-pin DIN serial port 704 as described above.

The user interface 112 has software for connecting with a barcodescanner 112 and decoding the barcode label 702 on the sensor 700 andmemory for storing the information read from the barcode. By scanningthe barcode with the barcode reader 800, the sensor specific informationis read and stored by the user interface 112. The sensor specificinformation is then accessible to the user interface 112 such that theuser interface 112 may use that information to calculate thesensor-specific response. When fluid or solution is passed through thefluid conduit 706, the user interface 112 collects analog measurementsfrom the sensor. The user interface 112 then uses this raw analog dataalong with the sensor-specific calibration factor (i.e. the CellConstant) and the temperature offset factor (TempOffset) obtained fromthe barcodes to calculate the sensor-specific response (i.e. the actualconductivity of the fluid). As shown in FIG. 7 the calibration factor isprinted on the label as “CF 0.182” and the temperature offset is printedas “TO −0.6.”

Other types barcodes or marking conventions may be used other than thelinear barcodes as shown in FIG. 7. For example multidimensionalbarcodes, 2D barcodes or matrix codes may be used in place of the linearbarcodes. The barcodes may also be affixed or etched on portions otherthan the sensor housing, such as on the fluid conduit 706 or theshipping bag or container.

An important sensor design consideration is accessibility of the sensoranalog circuitry (for example, the circuit connected to the thermistorand electrodes) by the user interface 112, even when the sensor memorydevice is non-functional or destroyed. Experimentation by the applicantsuggests that the analog circuitry of the sensor as depicted in FIGS.2-6 is unaffected by gamma or electron-beam irradiation. Thus,separation of analog circuits and digital circuits (i.e. circuits to thememory device) of the sensor is desirable. By separating the analog anddigital circuits, the analog circuits maintain functionality and canprovide the user-interface 112 with raw data.

As gamma or electron-beam irradiation renders the memory chip or EEPROMnon-functional, it is contemplated that sensor units may be manufacturedwithout memory chip. In these embodiments, the analog components aremanufactured and assembled into sensors. The sensors are validated andthe sensor specific information is then printed on the sensors orshipping bags in print or barcode form. The sensors are then placed inshipping bags or other suitable containers, irradiated via gamma rays orelectron-beam, and then delivered to the user. The sensor specificinformation is entered into the user-interface 112 either by a barcodescanner 800 as shown in FIG. 8, or manually by the user. This embodimentsaves the costs associated with the including the memory chip with thesensor.

The present invention also incorporates the method of preparing a sensorfor use in bio-pharmaceutical industry. As shown in FIG. 9, the sensorsare first manufactured. The sensors may be manufactured to includeanalog and/or digital circuits. The analog circuits may be used for datacollection purposes, while the digital circuits may be used to storesensor specific information. The sensors are then calibrated andvalidated using the techniques mentioned above and/or those known in theart. The sensor specific information obtained during the calibration andvalidation steps is then stamped or printed on the sensor in the form ofa barcode or other readable form. If the sensor includes a memory chip,the sensor specific information is also stored on the memory chip. Thesensor is then placed in a shipping bag or other container 908. Thecontainer and/or the sensor are then sterilized by autoclaving,time-limited exposure to an ethylene oxide gas, gamma ray irradiation,electron-beam irradiation, or by any other method known in the art 910.The sensor and container are then stored until they are deliver to theuser 912. The user then removes the sensor from the shipping bag orother container 914. The user then connects the sensor to the userinterface 916. If the sensor includes a memory chip containing sensorspecific information, the user interface downloads that information 918.Otherwise, the user uses a barcode scanner connected to the userinterface to read and enter the information into the user interface 920or enters the sensor specific information found on the label 922. Eitherbefore or after entering the sensor specific information, the sensor isconnected to the in-line system, closed-circuit or fluid transfer system924. The user interface and the sensor are then used to collect data926, such as conductivity, from the fluid passing through the system.Because the sensors are designed to be disposable, at the end of itslife cycles the sensors may be destroyed, thrown out, or recycled.

The aforementioned embodiments include a selection of novel sensormaterials, innovative circuit designs which separate the analog anddigital circuits, labeling to preserve sensor-specific information, anda user interface that includes supporting software and procedures toaccommodate, retrieve, interpret and calculate sensor-specificinformation. These materials, circuits, and labeling, are designed towithstand the conditions of the sterilization methods used by thebio-pharmaceutical industry.

It will be understood that the embodiments of the present inventionwhich have been described are illustrative of some of the applicationsof the principles of the present invention. Numerous modifications maybe made by those skilled in the art without departing from the truespirit and scope of the invention.

1-10. (canceled)
 11. A disposable sensor for measuring the conductivityof a bio-processing fluid, comprising: a conduit for directing abio-processing fluid; a sensing portion, said sensing portion beingarranged for sensing conductivity of bio-processing fluid passingthrough said conduit, said sensing portion having a structure formeasuring the temperature; a barcode printed or etched on the disposablesensor; and said apparatus is made of inexpensive disposable materialsuitable for single use of the apparatus.
 12. The sensor of claim 11,wherein said barcode is a matrix barcode.
 13. The sensor of claim 11,wherein said barcode contains calibration information including astatistical performance value based on individual measurementperformances of a plurality of said disposable sensors.
 14. The sensorof claim 11, wherein said sensing portion comprises a printed circuitboard.
 15. The sensor of claim 11, wherein said structure for measuringthe temperature of the bio-processing fluid includes at least onethermistor.
 16. The sensor of claim 11, wherein said sensing portion iscomposed of at least one electrode being arranged such that same is incontact with said bio-processing fluid during use of the apparatus. 17.The sensor of claim 16, wherein said sensing portion is composed of fourelectrodes being arranged such that said electrodes are in contact withsaid bio-processing fluid during use of the apparatus.
 18. The sensor ofclaim 11, further comprising a user interface, said user interface beingconnectable with said sensing portion.
 19. The sensor of claim 18,wherein said user interface drives a current through the sensingportion, and said user interface is able to calculate the conductivityof the bio-processing fluid.
 20. The sensor of claim 18, wherein saiduser interface has the ability to access or retrieve the data encoded bysaid barcode.
 21. The sensor of claim 11, wherein said barcode is amultidimensional barcode, said barcode being able to encode calibrationdata, said sensing portion having four electrode pins, and saidelectrode pins being arranged such that they are in contact withbio-processing fluid passing through said conduit, at least a portion ofsaid conduit and said sensing portion being arranged within aimpermeable housing.
 22. The sensor of claim 11, wherein said sensingportion also has a memory component.
 23. The sensor of claim 22, whereinsaid memory component stores calibration information including astatistical performance value based on individual measurementperformances of a plurality of said disposable sensors.
 24. The sensorof claim 22, wherein said memory component is a non-volatile memorychip.
 25. The sensor of claim 22, wherein said memory component storesor contains at least the same information as encoded by said barcode.26. The sensor of claim 25, wherein said component stores or containsadditional calibration information not encoded by said barcode. 27-30.(canceled)
 31. The sensor of claim 22, wherein said memory component isa non-volatile memory chip.
 32. The sensor of claim 31, wherein saidnon-volatile memory chip is an EEPROM.
 33. A user interface forconnecting to disposable sensor, comprising: hardware input and outputconnections for connecting to a barcode scanner; hardware input andoutput connections for connecting to a disposable sensor, said sensorwhen activated returns analog signals through said hardware connectionsto the user; software for interpreting said analog signals; software fordecoding barcodes read by said barcode scanner; memory for storing saidsoftware for interpreting, software for decoding, and informationdecoded by the software for decoding barcodes.
 34. The user interface ofclaim 33, further comprising: a display for displaying informationrelated to said analog signals return from said disposable sensor. 35.The user interface of claim 33, wherein said memory component is anon-volatile memory chip.
 36. The user interface of claim 35, whereinsaid non-volatile memory chip is an EEPROM.